Neoadjuvant Phase II Trial in Patients With T1c Operable, HER2-positive Breast Cancer According to TOP2A Status

NCT02339532 | Completed Phase 2 DMC

• 1 other identifier: GEP13
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 12

Brief Summary

The main objective of this multicenter study will therefore be to evaluate pathologic complete response rates of an anthracycline-based regimen \[FEC 100 - TAXOTERE® - HERCEPTIN® - PERTUZUMAB\] and a non anthracycline-based regimen \[TAXOTERE® - CARBOPLATINE - HERCEPTIN® - PERTUZUMAB\] according to the presence or not of TOP2A gene amplification in a population of breast cancer patients with HER2 overexpression. A very important objective of the study will be the evaluation of biomarkers that predict response to treatment.

Conditions

Breast Cancer

Keywords

HER2-positive; non-metastatic; TOP2A

Outcome Measures

Primary Outcomes (1)

• Pathological complete response according to Chevallier classification

  on surgical specimen and lymph nodes at the time of the surgery

  20 weeks

Secondary Outcomes (6)

• Predictive factors of response to both treatment regimens (anthracycline-based and non anthracycline-based regimens)

  20 weeks

• Pathological complete response (pCR), according to Sataloff's classification

  20 weeks

• Clinical and radiological response according to the WHO criteria

  after two cycles of treatment and after the end of treatment

• Toxicity according to NCI CTC-AE v4.0 criteria

  during on-treatment period (defined as the period from the first dose of study medication up to 30 days of the last dose

• Progression-free survival

  up to 60 months

Study Arms (2)

TOP2A amplified

EXPERIMENTAL

If TOP2A amplified: FEC x 3 then THP x 3 3 cycles of FEC 100 administered IV q3w * 5-Fluorouracil (5-FU) 500 mg/m² * Epirubicin 100 mg/m² * Cyclophosphamide 500 mg/m² Followed by 3 cycles of Trastuzumab-Pertuzumab-Docetaxel: * Trastuzumab 8 mg/kg loading dose administered intravenously (IV) followed by 6 mg/kg IV q3w in subsequent cycles. * Pertuzumab 840 mg loading dose administered IV followed by 420 mg IV q3w in subsequent cycles. * DOCETAXEL 75 mg/m² IV escalating at 100 mg/m² IV as tolerated q3w

Drug: FEC100; Drug: Docetaxel; Drug: Trastuzumab; Drug: Pertuzumab

TOP2A not amplified

EXPERIMENTAL

If TOP2A not amplified: TCHP x 6 TCHP administered IV q3w for 6 cycles * Trastuzumab 8 mg/kg loading dose administered IV followed by 6 mg/kg IV q3w in subsequent cycles. * Pertuzumab 840 mg loading dose administered IV followed by 420 mg IV q3w in subsequent cycles. * DOCETAXEL 75 mg/m² IV q3w * CARBOPLATIN AUC 6 IV q3w The Calvert formula will be used to calculate the dose of carboplatin: Dose (mg) = target AUC (mg/mL x min) x \[GFR mL/min + 25\] Dose (mg) = 6 x \[GFR mL/min + 25\] NOTE: the Calvert formula gives the dose in mg, not mg/m². GFR, glomerular filtration rate The maximum dose of CARBOPLATIN must not exceed 900 mg.

Drug: Docetaxel; Drug: Trastuzumab; Drug: Pertuzumab; Drug: Carboplatin

Interventions

FEC100 DRUG

3 cycles of FEC 100 administered IV q3w * 5-Fluorouracil (5-FU) 500 mg/m² * Epirubicin 100 mg/m² * Cyclophosphamide 500 mg/m²

TOP2A amplified

Docetaxel DRUG

TOP2A amplified : DOCETAXEL 75 mg/m² IV escalating at 100 mg/m² IV as tolerated q3w TOP2A not amplified : DOCETAXEL 75 mg/m² IV

TOP2A amplified; TOP2A not amplified

Trastuzumab DRUG

Trastuzumab 8 mg/kg loading dose administered intravenously (IV) followed by 6 mg/kg IV q3w in subsequent cycles.

TOP2A amplified; TOP2A not amplified

Pertuzumab DRUG

Pertuzumab 840 mg loading dose administered IV followed by 420 mg IV q3w in subsequent cycles.

TOP2A amplified; TOP2A not amplified

Carboplatin DRUG

CARBOPLATIN AUC 6 IV q3w

TOP2A not amplified

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women aged ≥ 18;
• Patient has histologically confirmed breast cancer, with a clinical tumour diameter of \> 1 cm (cT1c, cT2-3 or T4a)-
• Any N status
• No clinically or radiologically detectable metastases (M0);
• HR negative (both ER and PR \< 10% by IHC); for T1c status, otherwise HR negative or positive
• Her-2 positive (i.e. IHC score 3+ or FISH/SISH/CISH positive);
• Performance status ≤ 1 (according to WHO criteria);
• Patients not previously treated by surgery, radiotherapy, hormone therapy or chemotherapy;
• Hæmatology: Absolute neutrophil count (ANC) ≥1,500/mm³; Platelets ≥100,000/mm³; Total white blood cell count (WBC) ≥3.000/mm³; Hb\> 9g/dl;
• Hepatic Function: Total bilirubin ≤1.5 time the upper normal limit (UNL); ASAT ≤ 1.5xUNL; ALAT ≤ 1.5xUNL; Alkaline phosphatase ≤ 2.5xUNL;
• Renal Function: Serum creatinine ≤1.5xUNL (and if Serum creatinine \>1.5xUNL, Creatinine clearance ≥50 mL/min (MDRD formula);
• Metabolic Function: Magnesium ≥ lower limit of normal; Calcium ≥ lower limit of normal;
• Patient agreeing to use effective contraception during and for ≥ 7 months after completion of study treatment;
• Patient able to comply with the protocol;
• Patient must have signed a written informed consent form prior to any study specific procedures;

You may not qualify if:

• Bilateral or multifocal breast cancer;
• Non-measurable tumour;
• HER2 negative status (i.e. IHC score 0 or 1+, or IHC score 2+ and FISH/SISH/CISH negative);
• RH positive (ER or PR ≥ 10% by IHC) ;
• Patient has a history of second cancer, with exception of in situ cervical cancer or basocellular skin cancer which is regarded as cured;
• Patient has already been treated for new breast cancer;
• Patients have already undergone surgery for their disease or have had primary axillary dissection;
• Prior docetaxel administration or anti-HER2 antibody therapy (e.g.: trastuzumab or pertuzumab);
• Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, such as, but not limited to:
• Heart or kidney failure, medullary, respiratory or liver failure, dyspnea
• Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia, poorly controlled hypertension) ≤ 1 year before enrollment
• Uncontrolled diabetes
• Significant neurological or psychiatric abnormalities
• Symptomatic or progressive disorder of the central nervous system (CNS) or metastasis at the initial check-up.
• Peripheral neuropathy \> grade 2

Sponsors & Collaborators

• UNICANCER: lead

Study Sites (12)

Institut de Cancerologie de L'Ouest - Site Paul Papin

Angers, France

Location

Centre Hospitalier Regional Universitaire de Brest - Hôpital Morvan

Brest, France

Location

Centre Francois Baclesse

Caen, France

Location

Centre Jean Perrin

Clermont-Ferrand, France

Location

Chu de Grenoble - Hopital Michallon

Grenoble, France

Location

Chu de Limoges - Hôpital Dupuytren

Limoges, France

Location

Centre Leon Berard

Lyon, France

Location

Institut Regional Du Cancer Montpellier Val D'Aurelle

Montpellier, France

Location

Institut de Cancerologie de L'Ouest - Site Rene Gauducheau

Saint-Herblain, France

Location

Hopital D'Instructions Des Armees

Saint-Mandé, France

Location

Centre Paul Strauss

Strasbourg, France

Location

Institut de Cancerologie de Lorraine Alexis Vautrin

Vandœuvre-lès-Nancy, France

Location

Related Publications (1)

• Ginzac A, Molnar I, Durando X, Motte Rouge T, Petit T, D'hondt V, Campone M, Bonichon-Lamichhane N, Venat Bouvet L, Levy C, Augereau P, Pistilli B, Arsene O, Jouannaud C, Nguyen S, Cayre A, Tixier L, Mahier Ait Oukhatar C, Nabholtz JM, Penault-Llorca F, Mouret-Reynier MA. Neoadjuvant anthracycline-based (5-FEC) or anthracycline-free (docetaxel/carboplatin) chemotherapy plus trastuzumab and pertuzmab in HER2 + BC patients according to their TOP2A: a multicentre, open-label, non-randomized phase II trial. Breast Cancer Res Treat. 2024 Jun;205(2):267-279. doi: 10.1007/s10549-024-07285-y. Epub 2024 Mar 7.

  PMID: 38453781 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Docetaxel; Trastuzumab; pertuzumab; Carboplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes

Study Officials

• Marie-Ange MOURET REYNIER

  Centre Jean Perrin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2014
• First Posted: January 15, 2015
• Study Start: January 1, 2015
• Primary Completion: October 7, 2019
• Study Completion: July 8, 2024
• Last Updated: November 8, 2024

Record last verified: 2024-11

Locations

FR (12)